Process for the preparation of 2-substituted 5-alkyl-pyridines

Abstract

The title compounds of the formula ##STR1## can be prepared by cyclization of aminomethylenated 2-pentenoic acid derivatives of the formula ##STR2## where R, X, R 1 , R 2 and Z have the meaning given in the description, in the presence of acids or ammonia. Preferably, aminomethylenated pentenoic acid derivatives are employed which can be prepared from pentenoic acid derivatives of the formula R--CH.sub.2 --CH.sub.2 --CH═CH--Z (III) or R--CH.sub.2 --CH═CH--CH.sub.2 --Z (IV) with ortho-amides of the formula ##STR3## The meanings of A and B are also given in the description.

We claim: 
     
       1. A process for the preparation of 2-substituted 5-alkyl-pyridines of the formula ##STR10## in which R represents hydrogen or straight-chain or branched C 1  -C 4  -alkyl and X denotes chlorine, bromine, hydroxyl or amino, wherein a aminomethylenated 2-pentenoic acid derivative of the formula ##STR11## in which R 1  and R 2  independently of one another represent straight-chain or branched C 1  -C 8  -alkyl, C 2  -C 8  -alkenyl, C 2  -C 8  -alkoxyalkyl, C 3  -C 8  -alkoxyalkenyl, C 3  -C 8  -cycloalkyl, C 6  -C 12  -aryl, C 7  -C 10  -aralkyl or a 5- to 8-membered saturated or unsaturated heterocyclic ring containing, 1 or 2 heteroatoms of which are selected from the group consisting of N, O and S, or where R 1  and R 2 , together with the N atom which they substitute, form a 5- to 8-membered ring which optionally contains a further heteroatom from the group consisting of N, O and S, and     Z represents CN or COOR 3 , where R 3  denotes straight-chain or branched C 1  -C 8  -alkyl, C 2  -C 8  -alkenyl, C 2  -C 8  -alkoxyalkyl, C 3  -C 8  -alkoxyalkenyl or C 3  -C 8  -cycloalkyl, are cyclized optionally in the presence of a polar solvent and in the presence of     1to 10 mol, relative to the 2-pentenoic acid derivative, of HCl;   HBr; or   a concentrated strong inorganic or organic non-oxidizing oxygen acid; or       1 to 10 mol, relative to the butene derivative, of NH 3 .   
     
     
       2. The process according to claim 1, wherein said aminomethylenated 2-pentenoic acid derivative used is obtained by the reaction of a non-aminomethylenated 2-pentenoic acid derivative of the formula   R--CH.sub.2 --CH.sub.2 --CH═CH--Z or R--CH.sub.2 --CH═CH--CH.sub.2 --Z     with an ortho-amide of the formula ##STR12## where A and B independently of one another represent OR 4 , OR 5 , N(R 6 ,R 7 ) or N(R 8 ,R 9 ), wherein R 4 , R 5 , R 6 , R 7 , R 8  and R 9  independently of one another have the meaning of R 1  or R 2 ,   in the presence or in the absence of a solvent whose acidity is lower than the C--H acidity of the 2-pentenoic acid derivative, at a temperature 50° to 200° C., and at a pressure 0.01 to 10 bar wherein the molar ratio of 2-pentenoic acid derivative to ortho-amide is 1 to 50:1.   
     
     
       3. The process according to claim 1, wherein R is hydrogen. 
     
     
       4. The process according to claim 1, wherein R 1  and R 2  independently of one another denote straight-chain or branched C 1  -C 8  -alkyl, cyclopropyl, cyclopentyl, cyclohexyl, phenyl or benzyl or together with the N atom which they substitute, form a 5- to 8-membered ring which optionally contains a further heteroatom from the group consisting of N, O and S. 
     
     
       5. The process according to claim 4, wherein R 1  and R 2  independently of another denote straight-chain or branched C 1  -C 4  -alkyl or together with the N atom which they substitute, form a morpholine, pyrrolidine or piperidine moiety, which is optionally substituted by C 1  -C 4  -alkyl or by hydroxy-C 1  -C 4  -alkyl. 
     
     
       6. The process according to claim 2, wherein the reaction is carried out at the boiling point of the 2-pentenoic acid derivative and is performed in an attached column with the ortho-amide being fed into said column. 
     
     
       7. The process according to claim 2, wherein the crude aminomethylenation product is cyclized. 
     
     
       8. The process according to claim 1, wherein the aminomethylated-2-pentenoic acid derivative is cyclized in the presence of HCl, HBr or a concentrated strong inorganic or organic non-oxidizing oxygen acid.